1994 Fiscal Year Final Research Report Summary
Role of anti-HIV-gp120 antibody in the lpr^<cg> and other autoimmune mice.
Project/Area Number |
05670411
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
内科学一般
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Research Institution | The University of Tokyo |
Principal Investigator |
KIMURA Mikio The University of Tokyo, The Institute of Medical Science, Clinical Associate, 医科学研究所, 助手 (90114462)
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Co-Investigator(Kenkyū-buntansha) |
NARIUCHI Hideo The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (10012741)
MATSUZAWA Akio The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (50012745)
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Project Period (FY) |
1993 – 1994
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Keywords | autoimmunity / lpr^<cg> gene / HIV / gp120 / idiotype network |
Research Abstract |
The novel mouse model for autoimmune disease CBA-lpr^<cg>/lpr^<cg>, which we found and established, carries the autosomal recessive gene lpr^<cg>. The gene is located on chromosome 19 at the same locus as lpr. In contrast to lpr, lpr^<cg> is complementary with gld which is located on chromosome 1. Because of this, lpr^<cg> has been a matter of interest that might enable to clarify the interrelationship between lpr or lpr^<cg> and gld in causing autoimmunity. From the studies with both bone marrow and lymph node transplantation, we have postulated that lpr or lpr^<cg> is a defect of a receptor and gld is a defect of its ligand. This hypothesis is verified by the discovery that the former is a defect of Fas antigen and the latter is a defect of its ligand. During investigations using this mouse model, we found that antibody was produced against HIV-gp120. Because gp120 has a molecular mimicry with MHC class II antigen, anti-gp120 might influence class II-bearing lymphocytes. Furthermore, if anti-anti-gp120 antibody as an antiidiotypic antibody is formed, it can influence CD4^+ lymphocytes because of the molecular mimicry between the antiidiotypic antibody and gp120. These antibodies may have vital roles for autoimmunity. Because the Western blot assay for anti-gp120 yielded negative results, we were forced to develop a highly sensitive EIA.The antibody was shown to be produced in various autoimmune mice. The highest titer was observed in the CBA-lpr^<cg>/lpr^<cg> but not in MRL-lpr^<cg>/lpr^<cg> that exhibited the highest degree of autoimmune disease. This implied that the antibody is not solely the result of autoimmunity and also revealed the difference of genetic backgrounds between CBA and MRL mice. Next, we attempted to get hybridoma producing anti-gp120 monoclonals. So far, it has not been successful and is now being continued.
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Research Products
(12 results)